One of the general objectives of the proposed research is to develop a new, efficient, and selective synthetic methodology applicable to the synthesis of a wide variety of organic compounds of medicinal and biological interest. To this end, carbometallation reactions involving late transition metal complexes, especially palladium complexes, as catalysts will be investigated and developed. In addition to those involving alkyl, lll, benzyl, alkenyl, aryl and alkynyl derivatives of palladium and other transition metals, addition reactions of acylpalladium (acylpalladation) and related derivatives will be developed. Since the majority of compounds of medicinal and biologically interesting compounds are cyclic, most of the efforts will be directed to the development of cyclic carbopalladation, cyclic acylpalladation, and related cyclization reactions. One of the main specific goals of the proposed research is to develop a conceptually novel "zipper"-mode cascade cyclization methodology based on cyclic carbopalladation, acylpalladation, and related reactions, which are expected to significantly expand the synthetic options and simplify the retro-synthetic analysis for preparing a wide variety of polyfused compounds. The second general objective is to actually demonstrate efficient and selective syntheses of organic compounds of medicinal and biological interest. The overall merit of such research activities transcends mere procurement of compounds of medicinal and biological importance. Besides being of medicinal and biological interest, the natural products dealt with in the proposed research are to help define the direction of the methodologial investigations and provide an indispensable means of critically evaluating their values. Indeed, the target compounds in the proposed research are primarily chosen from these latter viewpoints. Specifically, they include: nagilatone F, illudin M, sterpurene, frullanolide, paniculide A, nanaomycin A, daunomycinone aglycone, patulin, freelngyne, and 9Z-retinoic acid. Although not discussed in full detail, cortisone, jervine, rubrolides, and nostoclides will be considered as guides to methodological developments and potential future agents. Some final products as well as intermediates obtained in both methodological and application studies will be submitted for medicinal screening.